The growth of a tumor to clinically malignant dimensions requires angiogenesis, the sprouting of new blood vessels from pre-existing vasculature.[1-3] Not only is angiogenesis crucial for tumor growth due to oxygen and nutrient demands, it is also essential for the progression of tumor malignancy. Angiogenesis inhibitors, used either in conjunction with or in place of traditional cytotoxic chemotherapies, have shown promise in restricting tumor growth and have thus become a topic of much research. [4]
Due to the prohibitive cost of synthesizing and purifying protein therapeutics, peptides can potentially be clinical game-changers, especially if their activity and potency match that of whole protein. Rationally designed molecules that conjugate a bioactive peptide to a self-assembly region have shown much promise in mimicking the bioactivity of proteins. These molecules, known as peptide amphiphiles (PAs), typically consist of a hydrophobic alkyl tail, a peptide sequence capable of β-sheet formation, and the peptide.[13-15] Optionally there may be a flexible peptide sequence as linker between the peptide sequence capable of beta-sheet formation, and the peptide. PAs have been shown to self-assemble in aqueous solution into nanostructures, including high aspect-ratio nanofibers comprised of a hydrophobic core and stabilized by beta-sheet formation down the long axis.[16,17] These nanofibers can display a high surface density of peptides,[18] stabilize peptide secondary structure,[19] and improve therapeutic retention in tissue.[20,21] Thus, such PAs can be functionally protein-mimetic with regards to activity and potency. For example, protein-mimetic PAs bearing peptides derived from vascular endothelial growth factor and glucagon-like peptide 1 have shown remarkable bioactivity in stimulating angiogenesis and promoting insulin release, respectively.[19,22]